skeleton
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
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• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
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• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls
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• in the K/BXN serum-transfer arthritis model, mice exhibit a normal inflammatory response, as measured by hind paw swelling, but show significantly more inflammatory bone loss than wild-type controls, as determined by the reduction in remaining knee bone volume and increased % OcS/BS
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• mice develop osteopenia under basal conditions
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• at 16 weeks of age, females show a 35% decrease in trabecular bone volume per tissue volume in proximal femurs relative to wild-type controls
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• at 16 weeks of age, females show significant trabecular thinning in proximal femurs relative to wild-type controls
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• at 16 weeks of age, females show decreased bone mass under basal conditions
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• mutant BMMs cultured on bovine bone slices in the presence of M-CSF and RANKL for 10 days show a significant increase in % resorbed area relative to wild-type controls
• following supracalvarial LPS injection, mice develop marked focal osteolysis and increased osteoclast surface relative to wild-type controls
• however, the resorptive capacity of individual osteoclasts is not altered, as determined by plating committed osteoclasts (BMMs differentiated on plastic with M-CSF and RANKL for 3 days) on bovine bone slices for 48 hours
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immune system
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
|
• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
|
• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls
|
• in the K/BXN serum-transfer arthritis model, mice exhibit a normal inflammatory response, as measured by hind paw swelling, but show significantly more inflammatory bone loss than wild-type controls, as determined by the reduction in remaining knee bone volume and increased % OcS/BS
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hematopoietic system
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
|
• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
|
• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls
|
cellular
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
|